Screening for Flare After b/tsDMARD Discontinuation in Rheumatoid Arthritis

Sponsor

Medical University of Vienna (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05119452

Collaborator

Medical University of Graz (Other), Medical University Innsbruck (Other), Hospital Hietzing (Other), Krankenhaus Bruneck (Other)

Enrollment

Arms

30.1

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

To evaluate whether stringent follow-up consisting of combined laboratory and ultrasound surveillance is superior to clinical monitoring alone to maintain clinical remission in rheumatoid arthritis.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Other: Discontinuation of biological/targeted synthetic disease modifying anti-rheumatic drug (b/tsDMARD)	N/A

Detailed Description

Randomized, controlled, parallel-group, multi-centre study in which patients with rheumatoid arthritis treated with biological/targeted synthetic disease modifying antirheumatic drug (b/tsDMARD) in mono- or combination therapy with conventional synthetic disease modifying antirheumatic drug (csDMARD) in a stable dosage and interval for ≥6 months with low disease activity or remission will receive an power Doppler musculoskeletal ultrasound examination (PDUS) and monitoring of C-reactive protein (CRP) levels at baseline and several timepoints within a 24 month study period (primary endpoint) and within a 48 month long-term extension. At baseline, b/tsDMARD medication will be withdrawn in all patients, who will be randomized in a 1:1 ratio in an "Assisted monitoring" (arm A) or a "Clinical monitoring" (arm B) arm respectively. Further stratification for remission vs. low disease activity and mono- vs combination therapy will be implemented in the randomisation process. In arm A, CRP and PDUS information will be made available to the clinical assessors who, at each time-point will use this information along with that from clinical examination, to identify patients experiencing recurrence of inflammation which will then be counted as subclinical flare according to predefined criteria. In arm B the results of CRP and PDUS will be recorded but will not be made available to the clinical assessor who will have to identify clinical flares according to predefined criteria based on information from the clinical examination only.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

85 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

At baseline, patients will be randomised in a 1:1 ratio in an "Assisted monitoring" (arm A) or a "Clinical monitoring" (arm B) arm respectively.At baseline, patients will be randomised in a 1:1 ratio in an "Assisted monitoring" (arm A) or a "Clinical monitoring" (arm B) arm respectively.

Masking:

Double (Participant, Investigator)

Masking Description:

After checking the inclusion- and exclusion criteria and after the patients´ consent the study investigator contacts the administrative office of the coordinating center. The online computerised randomisation algorithm "Randomizer for Clinical Trials by the Medical University of Vienna (MUW) will be used for randomisation for all centres.

Primary Purpose:

Other

Official Title:

Screening for Flare After Discontinuation of Biological/Targeted Synthetic Disease Modifying Anti-rheumatic Drug (b/tsDMARD) in Rheumatoid Arthritis

Anticipated Study Start Date :

Mar 1, 2022

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Sep 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Other: Assisted monitoring In the Assisted monitoring arm, C-reactive protein and musculoskeletal ultrasound information will be made available to the clinical assessors who, at each time-point will use this information, along with information from the clinical examination, to identify patients experiencing recurrence of inflammation which will then be counted as subclinical flare according to predefined criteria.	Other: Discontinuation of biological/targeted synthetic disease modifying anti-rheumatic drug (b/tsDMARD) The biological/targeted synthetic disease modifying anti-rheumatic drug will be discontinued in both arms at baseline Other Names: b/tsDMARD: Adalimumab, Infliximab, Golimumab, Certolizumab pegol, Tocilizumab, Sarilumab, Etanercept, Anakinra, Filgotinib, Updacitinib, Tofacitinib, Baricitinib
Other: Clinical monitoring In the Clinical monitoring arm, the results of C-reactive protein and musculoskeletal ultrasound information will be recorded but will not be made available to the clinical assessor who at each time-point will make the decision on whether the patient is experiencing or has experienced a clinical flare according to predefined criteria based on information from the clinical examination.	Other: Discontinuation of biological/targeted synthetic disease modifying anti-rheumatic drug (b/tsDMARD) The biological/targeted synthetic disease modifying anti-rheumatic drug will be discontinued in both arms at baseline Other Names: b/tsDMARD: Adalimumab, Infliximab, Golimumab, Certolizumab pegol, Tocilizumab, Sarilumab, Etanercept, Anakinra, Filgotinib, Updacitinib, Tofacitinib, Baricitinib

Arm

Intervention/Treatment

Other: Assisted monitoring

In the Assisted monitoring arm, C-reactive protein and musculoskeletal ultrasound information will be made available to the clinical assessors who, at each time-point will use this information, along with information from the clinical examination, to identify patients experiencing recurrence of inflammation which will then be counted as subclinical flare according to predefined criteria.

Other: Discontinuation of biological/targeted synthetic disease modifying anti-rheumatic drug (b/tsDMARD)

The biological/targeted synthetic disease modifying anti-rheumatic drug will be discontinued in both arms at baseline

Other Names:

b/tsDMARD: Adalimumab, Infliximab, Golimumab, Certolizumab pegol, Tocilizumab, Sarilumab, Etanercept, Anakinra, Filgotinib, Updacitinib, Tofacitinib, Baricitinib

Other: Clinical monitoring

In the Clinical monitoring arm, the results of C-reactive protein and musculoskeletal ultrasound information will be recorded but will not be made available to the clinical assessor who at each time-point will make the decision on whether the patient is experiencing or has experienced a clinical flare according to predefined criteria based on information from the clinical examination.

Other: Discontinuation of biological/targeted synthetic disease modifying anti-rheumatic drug (b/tsDMARD)

The biological/targeted synthetic disease modifying anti-rheumatic drug will be discontinued in both arms at baseline

Other Names:

b/tsDMARD: Adalimumab, Infliximab, Golimumab, Certolizumab pegol, Tocilizumab, Sarilumab, Etanercept, Anakinra, Filgotinib, Updacitinib, Tofacitinib, Baricitinib

Outcome Measures

Primary Outcome Measures

Proportion of subjects without a clinical flare until week 24 [week 24]
Proportion of subjects without a clinical flare

Secondary Outcome Measures

Proportion of subjects without a clinical flare [week 48]
Proportion of subjects without a clinical flare
Time to clinical flare (days) [study period]
Time to clinical flare (days)
28 swollen joint count [week 24]
28 swollen joint count, scale 0 (best) - 28 (worse)
28 tender joint count [week 24]
28 tender joint count, scale 0 (best) - 28 (worse)
Proportion of subjects with a clinical flare in the assisted monitoring arm vs. clinical monitoring arm, the latter stratified according to b/tsDMARD reinitiation [week 24]
Proportion of subjects with a clinical flare in the assisted monitoring arm vs. clinical monitoring arm, the latter stratified according to b/tsDMARD reinitiation
Proportion of patients in low disease activity or remission based on simplified disease activity index [week 24]
Proportion of patients in low disease activity or remission based on simplified disease activity index
Proportion of patients in low disease activity or remission based on simplified disease activity index [week 48]
Proportion of patients in low disease activity or remission based on simplified disease activity index
Patient's global assessment [week 24]
Patient's global assessment, scale 0 (best) - 100 (worst)
Evaluator's global assessment [week 24]
Evaluator's global assessment, scale 0 (best) - 100 (worst)
C-reactive protein [week 24]
C-reactive protein, scale 0 (best) - infinite (worst)
Radiographic progression [at week 48 weeks from baseline]
change in Sharp Van der Heijde score, scale 0 (best) - 488 (worse)
Health Assessment Questionnaire Disability Index [week 24]
Health Assessment Questionnaire Disability Index, scale 0 (best) - 3.0 (worse)
World Health Organization Quality of Life Questionnaire [week 24]
World Health Organization Quality of Life Questionnaire, scale 0 (worse) - 100 (best)
Morning stiffness [week 24]
Morning joint stiffness, (minutes), scale 0 (best) - infinite (worst)
Fatigue [week 24]
Fatigue, visual analogue scale, scale 0 (worse) - 100 (best)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with rheumatoid arthritis classified by the American College of Rheumatology/European League Against Rheumatism classification criteria

biological disease-modifying anti-rheumatic drug (bDMARD) or targeted synthetic disease-modifying anti-rheumatic drug (tsDMARD) treatment in monotherapy or in combination therapy with conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) in a stable dosage and interval for ≥6 months. Previous extension of bDMARD or tsDMARD interval will also be accepted. bDMARDs and tsDMARDs will include all currently available originator and biosimilar compounds, with the exception of rituximab and its biosimilar compounds
No swollen joint by 28-joint count at baseline, and screening
C-reactive protein of ≤0.5mg/dL at baseline AND history of C-reactive protein

0,5mg/dl related to rheumatoid arthritis activity

Clinical disease activity index ≤10
Shared decision between patient and physician to attempt b/tsDMARD withdrawal
Willing and able to understand and follow the study procedures
Written informed consent
Female and male subjects aged ≥ 18 years

Exclusion Criteria:

History of or current extra-articular manifestation of rheumatoid arthritis, with exception of rheumatoid nodules
Systemic glucocorticoid treatment in the past 3 months
Intraarticular injection with glucocorticoids in the past 1 month
Joint replacement surgery other than total knee or hip arthroplasty or complete joint destruction
Power Doppler signal ≥2 in any assessed joint and/or tendon at screening or baseline